The film-coating applied to pharmaceutical preparations makes it possible to mask the bitter taste of the pharmaceuticals, to increase the hardness of the resulting pharmaceuticals and to impart a smooth surface to them. As bases for use in the film-coating treatment, there 20 have in general been employed, for instance, water-soluble cellulose ethers having a low degree of polymerization. The term "cellulose ethers having a low degree of polymerization" means cellulose ethers whose 2% aqueous solution has a viscosity of not more than 20 cSt (centistokes) as determined at 20.degree. C. and can be obtained by depolymerization of cellulose ethers having a high degree of polymerization.
The cellulose ethers having a high degree of polymerization can be prepared by converting purified pulp into an alkaline cellulose and then reacting the alkaline cellulose with an etherifying agent. After the etherification, the cellulose ether having a high degree of polymerization is refined with hot water, dried and then finely pulverized to an average particle size of the order of 50 .mu.m. The fine powder thus obtained is depolymerized. As depolymerization methods, there have been known, for instance, a method in which hydrogen chloride gas is used (Japanese Patent Publication No. 48-41037) and a method which comprises acting hydrogen peroxide on such fine powder (Japanese Patent Publication No. 45-678).
However, the cellulose ethers having a low degree of polymerization prepared by the foregoing methods have a tinge of gray or yellowish color and accordingly, if pharmaceuticals are film-coated with the cellulose ethers as bases, the pharmaceuticals seem to be colored due to the influence of the bases. For this reason, pharmaceuticals have currently been pigmented to impart good appearance to them by incorporating a coloring agent into the base upon film-coating the same. In this case, however, the color tone of the resulting pharmaceuticals is not clear due to the color of the base per se and the commercial value thereof is impaired. Therefore, the cellulose ethers having a low degree of polymerization as bases must have high whiteness.
To further improve the whiteness of the cellulose ethers, there have been proposed methods which comprise acting bisulfite ions (Japanese Patent Publication No. 46-41628) or sulfur dioxide (Japanese Patent Provisional Publication No. 52-152985) on the cellulose ethers in a water-soluble fatty acid alcohol to bleach or decolorize the same. However, these methods comprise complicated processes and sulfur-containing compounds remain in the resulting product as impurities. It has also been tried to improve the whiteness of the base by limiting the amount of water during reaction (Japanese Patent Provisional Publication No. 62-25101). However, this method cannot provide whiteness higher than a certain level.
The inventors of this invention have investigated the reason why the cellulose ethers having a low degree of polymerization are colored yellow or brown and taken note of the phenomenon that when the cellulose ethers having a high degree of polymerization are hydrolyzed with an acid, the yellow index of the cellulose ethers is increased simultaneously with a decrease in the viscosity thereof. The cellulose ether is dissolved in water to give a 2% aqueous solution thereof, the yellow index thereof is determined by SM Color Computer "SM-4" available from Suga Testing Machine Manufacturing Co., Ltd. and is used as the index for the whiteness.
FIG. 1 shows the relation between the wavelength of ultraviolet rays (NM) and the absorbance (A) of 2% aqueous solutions of cellulose ethers having different viscosities (3 cSt, 6 cSt and 500 cSt), the cellulose ether used being hydroxypropyl methyl cellulose. In FIG. 1, the absorbance shows two peaks in the vicinity of the UV wavelength of 230 and 280 nm. The lower the viscosity, i.e., the lower the degree of polymerization, the higher the absorbance at the peaks and, therefore, it can be assumed that a substance which has such peaks and becomes a cause of such a high yellow index is formed or present in a large amount in the cellulose ether having a low degree of polymerization.
The substance can be extracted from the hydroxypropyl methyl cellulose aqueous solution with diethyl ether. Moreover, it can be confirmed that the hydroxypropyl methyl cellulose aqueous solution from which the substance is removed by extraction has a reduced yellow index. However, the correct structure of the substance exhibiting such peaks has not yet been established. The substance is probably a product having chromophoric groups such as carbonyl and/or carboxyl groups formed through the oxidation of hydroxyl groups of the cellulose. It is also assumed that the glucose having groups formed through the modification of the cellulose due to oxidation is decomposed to give the substance capable of being extracted with the ether. The yellow index of an aqueous solution of the hydroxypropyl methyl cellulose from which this substance is extracted with ether is reduced, but it is still higher than that of the cellulose prior to the hydrolysis. This indicates that other chromophoric substances which cannot be extracted with ether would still remain in the aqueous solution of the hydroxypropyl methyl cellulose. Thus, there is a limit in the improvement of the whiteness by ether extraction. Furthermore, another extraction process is required for the preparation of cellulose ethers having a low degree of polymerization. The use of the ether extraction of the chromophoric substance in addition to the foregoing extraction process makes the production process complicated and thus is not proper.